tbuckley/cabot-search huggingface dataset:
Abstract 9590: Synergistic Effect of Lipoprotein (a) and C-reactive Protein on Prognosis of Familial Hypercholesterolemia
Authors: Hayato Tada, Nobuko Kojima, Kan Yamagami, Akihiro Nomura, Atsushi Nohara, Soichiro Usui, Kenji Sakata, Noboru Fujino, Masayuki Takamura, Masa-aki Kawashiri
Journal: Circulation (2022)

Background: The synergistic effect of lipoprotein (a) [Lp(a)] and C-reactive protein (CRP) on major adverse cardiovascular events (MACE) among patients with familial hypercholesterolemia (FH) is unknown. Objective: This study aimed to investigate the relations between Lp(a) and CRP levels and MACE in patients with FH whose Lp(a) levels are elevated. Methods: We retrospectively investigated associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and the occurrence of MACE among patients with FH (N = 786, male/female: 374/412). A Cox proportional hazard model was used to identify factors associated with MACE, adjusting for traditional risk factors. Patients with FH were divided into four groups, based on their Lp(a) and CRP levels, and assessed using Kaplan-Meier curves. Results: The median follow-up was 12.6 years (interquartile range [IQR], 9.5-17.9 years). During follow-up, 129 MACE were observed. Median Lp(a) and CRP levels were 21.4 (10.9-38.3) mg/dL and 0.20 (0.11-0.29) mg/dL, respectively. Under these conditions, natural log-transformed Lp(a) and CRP were not associated with MACE (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.91-1.25; P = 0.220; and HR, 1.12; CI, 0.96-1.28; P = 0.190, respectively). However, in Group 4, Lp(a) and CRP were significantly associated with MACE (HR, 2.44; CI, 1.42-3.46; P = 1.8 х 10 –7 ). Conclusion: In patients with FH, Lp(a) was significantly associated with MACE only when the CRP level was elevated. Patients with FH whose Lp(a) and CRP levels are elevated should be treated aggressively.
The association of female sex with management and mortality in patients with Staphylococcus aureus bacteraemia
Authors: Annette C. Westgeest, Felicia Ruffin, Jackson L. Kair, Lawrence P. Park, Rachel E. Korn, Maren E. Webster, Leo G. Visser, Emile F. Schippers, Mark G.J. de Boer, Merel M.C. Lambregts, Vance G. Fowler
Journal: Clinical Microbiology and Infection (2023)

ObjectivesThe association of biological female sex with outcome in patients with Staphylococcus aureus bacteremia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteremia.MethodsThis is a post-hoc analysis of prospectively collected data from the S. aureus Bacteremia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteremia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males.ResultsAmong 3384 patients with S. aureus bacteremia, 1431/3384 (42%) were females. Females were, as compared to males, more often black (581/1431 [41%] vs 620/1953 [32%], p <0.001), hemodialysis dependent (309/1424 [22%] vs 334/1940 [17%], p =0.001) and more likely to be infected with methicillin-resistant S. aureus (697/1410 [49%] MRSA in females vs 840/1925 [44%] MRSA in males, p =0.001). Females received shorter durations of antimicrobial treatment (median 24 [IQR 14-42] vs 28 [IQR 14-45] days, p =0.005), and were less likely to undergo transesophageal echocardiography) as compared to males (495/1430 [35%] vs 802/1952 [41%], p <0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in females vs 491/1953 [25%] in males, p = 0.204) or multivariable analysis (adjusted hazard ratio for females 0.98 [95% confidence interval 0.85-1.13]).ConclusionDespite significant differences in patient characteristics, disease characteristics, and management, females and males with S. aureus bacteremia have a similar mortality risk.
Endoscopic resection of a granular cell tumor (Abrikossoff’s tumor) in the esophagus using cap-assisted band ligation
Authors: Adrian Canavesi, Joaquín Berrueta, Sara Pillajo, Patricia Gaggero, Carolina Olano
Journal: Endoscopy (2023)

Granular cell tumors (GCTs), also known as Abrikossoff's tumors, are rare neoplasms of Schwann cell origin and are uncommon tumors of the esophagus [1] [2]. Depending on their clinical presentation, size, and location, these lesions may need to be resected, either surgically or endoscopically [3] [4] [5]. A 72-year-old woman with no past medical history of note was found to have a GCT of 10 mm in the esophagus. The patient wished the lesion to be resected.
Abstract 9373: Single Evaluation of Body Mass-Corrected Estimated Plasma Volume at Discharge Predicts Prognosis of Heart Failure Patients
Authors: Kazuhiro Kuroda, Masamichi Tanaka, Akihisa Yumoto, Soichiro Fuke
Journal: Circulation (2022)

Background: Estimated plasma volume(ePV) is a parameter of body fluid volume trends in the same patient and also an indicator for residual congestion. Patients with heart failure often have difficulty achieving adequate body fluid volume. We investigated the post-discharge prognosis of heart failure patients with a one-time evaluation of ePV at discharge corrected for body mass index (BMI). Methods: This is a single-center, prospective observational study. A total of consecutive 1268 heart failure hospitalizations, excluding acute coronary syndromes, from January 2018 to December 2021 were included. We evaluated 767 patients, excluding repeat hospitalizations of the same patient (366 cases), in-hospital deaths (54 cases), transfers for cardiac surgery and forced discharges (39 cases), and missing data (42 cases). A prognosis investigation was conducted for patients who haven’t visited our hospital for more than one year. BMI and ePV (ml, Hakim's formula) were calculated from height, weight, and hematocrit at discharge. Survival analysis was performed with ePV divided by BMI (ePV/BMI). Primary endpoint was composite of all-cause mortality and heart failure re-hospitalization. Results: median of 372 days of post-discharge observation, 205 deaths, and 336 composite endpoints were observed. ePV/BMI was categorized into three quartiles [low group (65.34-96.8), middle group (96.9-111.9) and high group (112.0-175.8)]. Survival analysis by ePV/BMI three tertiles showed a combined endpoint of death + rehospitalization (48.8 vs 69.2 vs 74.9%, log-rank P&lt;0.001) and death (11.7 vs 20.9 vs 24.7%, log-rank P&lt;0.001) at three years, respectively. Multivariable Cox proportional hazard model with covariant univariable predictive factors (age, severe kidney dysfunction, beta-blocker, angiotensin-converting enzyme inhibitor, psychotropic or cognitive medicines, in-hospital blood transfusion, low nutritional status) shows higher ePV/BMI tertile (HR1.44, 95%CI:1.26-1.64, p&lt;0.001), as well as the continuous variable of ePV/BMI (HR1.02, 95%CI:1.01-1.03, p&lt;0.001), is a predictive factor of the composite endpoint. Conclusion: Even after therapeutic intervention, ePV/BMI at discharge is a useful predictor of heart failure outcome.
The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment
Authors: Ming-Yue Fei, Yong Wang, Bin-He Chang, Kai Xue, Fangyi Dong, Dan Huang, Xi-Ya Li, Zi-Juan Li, Cheng-Long Hu, Ping Liu, Ji-Chuan Wu, Peng-Cheng Yu, Ming-Hua Hong, Shu-Bei Chen, Chun-Hui Xu, Bing-Yi Chen, Yi-Lun Jiang, Na Liu, Chong Zhao, Jia-Cheng Jin, Dan Hou, Xin-Chi Chen, Yi-Yi Ren, Chu-Han Deng, Jia-Ying Zhang, Li-juan Zong, Rou-Jia Wang, Fei-Fei Gao, Hui Liu, Qun-Ling Zhang, Ling-Yun Wu, Jinsong Yan, Shuhong Shen, Chun-Kang Chang, Xiao-Jian Sun, Lan Wang
Journal: Blood (2023)

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.
Abstract 9440: Acs in a Patient With Amegakaryocytic Thrombocytopenia: A Management Dilemma
Authors: Ashraf O Ahmed, Mohamed Abdelghani, Mohammad Abu-Tineh, Feryal Ibrahim, Mohammad Bakr, Alaa Rahhal, Abdulrahman Arabi
Journal: Circulation (2022)

Introduction: The management of Acute Coronary Syndrome (ACS) in thrombocytopenia is challenging. This abstract highlights the management dilemma of a patient who presented with high-risk ACS and was found to have Amegakaryocytic thrombocytopenia (AMT). Case Presentation: A fifty-five-year-old man with no cardiovascular risk factors was admitted with high-risk ACS with recurrent ischemic ECG changes and high troponin-T. He was found to have a low platelet count of 9 x10^3/uL. The initial impression was ACS and ITP. Course: No antiplatelet or anticoagulation was commenced. CT coronary angiography showed ostial left main (LM) severe stenosis. The patient received steroids and IVIG. A week later, cyclosporin and eltrombopag were added as the thrombocytopenia was refractory. Bone marrow biopsy showed AMT. His chest pain was persistent with ECG ischemic changes. A multidisciplinary team (MDT) decided that revascularization is urgently required, but the surgical option would have an extremely high bleeding risk. Alternatively, the Percutaneous option using radial access would have significantly less bleeding risk. However, he will need DAPT for at least the first week, which if interrupted, he will be at risk for stent thrombosis. The final decision was for platelet transfusion, then to proceed with the PCI once the platelet count is 50,000 or more, and to maintain the count &gt; 15,000 by transfusion whenever required. Management: After the targeted transfusion, the patient was started on aspirin and clopidogrel, then successful IVUS guided PCI to ostial LM with new generation DES was done via radial access and low therapeutic ACT range. Post PCI, the patient remained asymptomatic; he was observed as an inpatient for 14 days, during which he required platelet transfusion once when his platelet count dropped &lt; 15.000. DAPT was given for a week and then he was maintained on clopidogrel. In 3 months of follow-up, the patient had no cardiac complaints, no bleeding, and platelets were maintained between 15 to 30 on clopidogrel. Conclusion: ACS with severe thrombocytopenia is a management dilemma. Platelets transfusion, radial access, targeting low ACT, and using new generation stents for shorter DAPT duration might decrease the bleeding risk and thrombotic events.
Endoscopic omental packing in combination with the clip-and-snare method using pre-looping technique for gastric perforation
Authors: Naohiro Yoshida, Manami Utsunomiya, Azusa Kawasaki, Hiroyoshi Nakanishi, Shigetsugu Tsuji, Kenichi Takemura, Hisashi Doyama
Journal: Endoscopy (2023)

Endoscopic omental packing (EOP) is a technique used to close gastric perforations and is particularly useful for large defects [1]. We developed the pre-looping technique (PLT) as a simple and safe method of snare delivery into the stomach, and reported applications of the clip-and-snare method using PLT (CSM-PLT) as a traction method for endoscopic submucosal dissection (ESD) [2] [3]. We hereby describe a case where CSM-PLT was used for EOP during intraoperative perforation of gastric ESD.
Abstract 9243: Brain-Targeted Mechanical Intervention Using Passive Head Motion Can Have an Antihypertensive Effect
Authors: Yasuhiro Sawada, Naoyoshi Sakitani, Takahiro Maekawa, Daisuke Yoshino, Kouji Takano, Keisuke Shinohara, Takuya Kishi, Ayumu Konno, Hirokazu Hirai, Makoto Ayaori, Hirohiko Inanami, Koji Tomiyasu, Toru Ogata, Hirotsugu Tsuchimochi, Shinya Sato, Shigeyoshi Saito, Kohzoh Yoshino, Kenichi Funamoto, Hiroki Ochi, Masahiro Shinohara, Motoshi Nagao
Journal: Circulation (2022)

Introduction: Exercise is known to be effective as a therapeutic/preventative measure for numerous physical disorders and diseases including hypertension. However, the mechanisms underlying the antihypertensive effect of exercise remain to be elucidated. Hypothesis: The positive effects of exercise may be mediated by mechanical forces generated during exercise activities. Exercise-mimicking mechanical intervention may have an antihypertensive effect. Methods: We conducted animal experiments in which we reproduced mechanical accelerations generated in the head during moderate-velocity running. We performed in vitro experiments using cultured cells to determine what type of mechanical force was responsible for the antihypertensive effect of mechanical intervention. We carried out clinical studies to validate the clinical relevance of our findings. Results: Passive head motion (PHM) in hypertensive rats, which reproduced the mechanical accelerations generated in their heads during moderate-velocity treadmill running, decreased the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in the rostral ventrolateral medulla (RVLM), thereby lowering their blood pressure. PHM generated interstitial fluid movement that was estimated to exert shear stress with an average magnitude of &lt;1 Pa on the cells in the rat medulla. Fluid shear stress of a sub-Pa magnitude decreased the AT1R expression in cultured astrocytes. Inhibition of interstitial fluid movement following hydrogel introduction to the RVLM eliminated the antihypertensive effects of PHM and treadmill running. Vertically oscillating chair riding by hypertensive adult humans, which reproduced the mechanical accelerations generated in their heads during light jogging, lowered their blood pressure. Conclusion: Brain-targeted mechanical intervention can have an antihypertensive effect by modulating the function of RVLM astrocytes through interstitial fluid shear stress.
Abstract 285: Traditional Cardiopulmonary Resuscitation In Cardiac Arrest For Patients On Venovenous Extracorporeal Membrane Oxygenation
Authors: Erin G Roberts, Mazen F Odish, Gabriel Wardi, Cassia yi, Erica Pentony, Rebecca Sell
Journal: Circulation (2022)

Introduction: Mortality for patients on VV-ECMO remains high despite increased use during the COVID-19 pandemic. Unlike VA-ECMO which provides life support for cardiac failure and can be used as a bridge to definitive therapy during cardiac arrest (e-CPR), patients who arrest while on VV-ECMO currently may undergo traditional cardiopulmonary resuscitation (CPR). This poses many challenges such as potential cannula position disruption of the VV-ECMO system during compressions and it is unclear if patients on VV-ECMO will benefit from being offered traditional CPR. Hypothesis: Traditional CPR is effective in patients who arrest while on VV-ECMO. Methods: A retrospective chart review of inpatient cardiac arrest data from a high-volume ECMO center was performed. Patients who arrested while on VV-ECMO were included. Data including demographics, etiology of arrest, return of spontaneous circulation (ROSC) and survival to discharge were reviewed. Survival data was compared with the ECLS International Summary of Statistics. Results: We identified 19 patients on VV-ECMO who underwent CPR for cardiac arrest between September 2012 and November 2021. The average age of the patients was 42.7 years and 89.5% (n=17) were men. Seven of the nineteen total patients (36.8%) were being treated for ARDS from COVID-19 pneumonia. The arrest occurred on average 35.6 days into hospitalization (range: 1-132 days). The initial rhythm was pulseless electrical activity in 13 patients (68.4%), and the etiologies of arrest included hypoxemia (n=10, 52.6%), ECMO machine failure or during oxygenator exchange (n=3, 15.8%), pneumothorax (n=2, 10.5%), and cardiac tamponade (n=1, 5.3%). ROSC occurred in all 19 patients (100%), however only 4 patients (21.1%) survived to discharge with good neurologic recovery. Survival to discharge for all-comers on VV-ECMO is 66%. Conclusions: While there is limited evidence for the effectiveness of traditional CPR for patients on VV-ECMO, in this sample, ROSC was universal and one-fifth of patients survived to discharge. Future studies should continue to study the utility of CPR on VV-ECMO and how to optimize technique to improve outcomes for these critically-ill patients.
Abstract 15151: Identification of Novel Right Ventricular Function Phenotypes in Pulmonary Arterial Hypertension Using Unbiased K-Means Clustering
Authors: Rebecca R Vanderpool, Alexandra M Janowski, Charles Fauvel, Zilu Liu, Shili Lin, Priscilla Correa-Jaque, Amy Webb, Manreet Kanwar, Jidapa Kraisangka, Puneet Mathur, Adam Perer, Allen D Everett, Scott H Visovatti, Raymond L Benza
Journal: Circulation (2022)

Introduction: Survival in pulmonary arterial hypertension (PAH) is associated with right ventricular (RV) function rather than pulmonary vascular resistance (PVR). At present, RV function is not incorporated in current risk assessment models and studies evaluating RV function are generally limited to single-center studies. The aim was to identify novel RV function phenotypes using unbiased k-means clustering in patients with PAH. Methods: Baseline clinical and hemodynamic data in patients with PAH were harmonized data from 5 PAH clinical trials (COMPASS3: n=98, EARLY: n=176, GRIPHON: n=720, MAESTRO: n=44, and SERAPHIN: n=728). Pearson correlation analysis was used to select variables that reduce the co-linearity (|r| &lt; 0.7) between hemodynamic variables used in the models. K-means clustering methods were applied to advanced RV hemodynamics including end-systolic pressure (ESP), arterial elastance (Ea), single-beat end-diastolic elastance (Eed), Pulse pressure (PP), stroke volume (SV) and RV stroke work (RVSW). Survival analysis was used to compare all-cause mortality among each cluster group. Results: Participants in the harmonized dataset (n=1766) had a mean PAP of 53 ± 17 mmHg, a cardiac output of 4.3±1.4 L/min, a wedge pressure of 9±4 mmHg and a PVR of 11.8±7.4 WU. K-means clustering identified four distinct RV cluster phenotypes that range from mild to severe RV dysfunction (Fig. A). Participants in RV cluster 1 (RV C1) have severe RV dysfunction with increased pressure/afterload, decreased cardiac function, and increased diastolic stiffness compared to RV cluster 4 (RV C4). (Fig. A) RV C1 had decreased six-minute walk distance compared to other clusters. RVC1 and RVC2 had increased risk of mortality compared to RV C4 (Fig. B). Conclusion: Applying K-means clustering to harmonized hemodynamic data from PAH clinical trial data identified 4 unique RV function phenotypes with different clinical outcomes.
Abstract 15203: Single Cell Transcriptional Analysis Implicates <i>Acta2</i> Positive Pericytes in Arterial Muscularization and Imbalance in Bmp and Angpt Signaling During Development of Pulmonary Arterial Hypertension
Authors: Nicholas D Cober, Emma McCourt, Rafael Soares Godoy, Yupu Deng, Ken Schlosser, David Cook, Liyuan Wang, Duncan J Stewart
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is a lethal disease characterized by marked vascular remodeling, inflammation and increased pulmonary vascular resistance. Pericytes normally play a key role in maintaining microvascular homeostasis; however, they can also contribute to increased muscularization of distal arterioles in PAH by giving rise to smooth cells (SMCs). Methods: Sprague-Dawley rats were injected with 20mg/kg SU subcutaneously and exposed to 3 weeks of chronic hypoxia (CH, 10% O2). Right ventricular systolic pressure (RVSP) was measured at baseline, 1, 3, 5, and 8-weeks, then lungs were explanted, digested, and dissociated into single cells which were sequenced using the 10x genomics platform. Results: RVSP was significantly elevated at 1 week after SU (47mmHg) reaching a plateau of &gt;100 mmHg by 5 weeks. Dimensionality reduction of the scRNAseq data was performed using Uniform Manifold Approximation and Projection (UMAP) analysis resulting in 24 lung clusters and sub-clustering of stomal populations yielded seven clusters. In addition to fibroblasts, SMC/myofibroblasts and mesothelial cells, we identified 2 distinct pericyte clusters both expressing canonical pericyte markers such as Pdgfrb and Csgp4 ( Ng2 ) and differentiated by presence or absence of Acta2 . Acta2 + pericytes exhibited high expression of contractile markers (i.e., Myh11 and Tagln ), consistent with partial SMC differentiation, and underwent a substantial (&gt;3-fold) expansion during PAH development. The Acta2 + pericytes also exhibited profound downregulation in the endothelial protective gene, Bmpr2 , with a reciprocal upregulation of Rbpms2 , a gene which inhibits BMP signaling. Similarly, reciprocal reduction in Angpt1 , an agonist of the endothelial Tie2 receptor and an increase in expression the partial Tie2 antagonist, Angpt2 , thereby favoring EC activation and inflammation. Conclusion: These results suggest expansion of Acta2 + pericytes in PAH may contribute to distal arteriolar muscularization as well as an imbalance in BMP/TGFß and ANGPT1/2 signaling, promoting EC apoptosis, activation, and inflammation in the SU/CH model.